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Author |
Weick, J.P. |
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Title |
Functional Properties of Human Stem Cell-Derived Neurons in Health and Disease |
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Journal Article |
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Year |
2016 |
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Stem Cells International |
Abbreviated Journal |
Stem Cells Int |
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2016 |
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4190438 |
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Stem cell-derived neurons from various source materials present unique model systems to examine the fundamental properties of central nervous system (CNS) development as well as the molecular underpinnings of disease phenotypes. In order to more accurately assess potential therapies for neurological disorders, multiple strategies have been employed in recent years to produce neuronal populations that accurately represent in vivo regional and transmitter phenotypes. These include new technologies such as direct conversion of somatic cell types into neurons and glia which may accelerate maturation and retain genetic hallmarks of aging. In addition, novel forms of genetic manipulations have brought human stem cells nearly on par with those of rodent with respect to gene targeting. For neurons of the CNS, the ultimate phenotypic characterization lies with their ability to recapitulate functional properties such as passive and active membrane characteristics, synaptic activity, and plasticity. These features critically depend on the coordinated expression and localization of hundreds of ion channels and receptors, as well as scaffolding and signaling molecules. In this review I will highlight the current state of knowledge regarding functional properties of human stem cell-derived neurons, with a primary focus on pluripotent stem cells. While significant advances have been made, critical hurdles must be overcome in order for this technology to support progression toward clinical applications. |
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Department of Neurosciences, University of New Mexico Health Science Center, Fitz Hall Room 145, 915 Camino de Salud NE, Albuquerque, NM 87131, USA |
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1687-966X |
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PMID:27274733; PMCID:PMC4870377 |
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16675 |
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Ye, P.; Peyser, B.D.; Pan, X.; Boeke, J.D.; Spencer, F.A.; Bader, J.S. |
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Gene function prediction from congruent synthetic lethal interactions in yeast |
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Journal Article |
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2005 |
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Molecular Systems Biology |
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1 |
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1 |
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4100034 |
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Nature Publishing Group |
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refbase @ admin @ Congruence |
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12012 |
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Pfaender, S.; Fohr, K.; Lutz, A.-K.; Putz, S.; Achberger, K.; Linta, L.; Liebau, S.; Boeckers, T.M.; Grabrucker, A.M. |
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Title |
Cellular Zinc Homeostasis Contributes to Neuronal Differentiation in Human Induced Pluripotent Stem Cells |
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Journal Article |
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Year |
2016 |
Publication |
Neural Plasticity |
Abbreviated Journal |
Neural Plast |
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2016 |
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3760702 |
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Apoptosis/physiology; Cell Survival/physiology; Homeostasis/*physiology; Humans; Induced Pluripotent Stem Cells/cytology/*metabolism; Neurogenesis/*physiology; Neurons/cytology/*metabolism; Signal Transduction/physiology; Zinc/*metabolism |
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Disturbances in neuronal differentiation and function are an underlying factor of many brain disorders. Zinc homeostasis and signaling are important mediators for a normal brain development and function, given that zinc deficiency was shown to result in cognitive and emotional deficits in animal models that might be associated with neurodevelopmental disorders. One underlying mechanism of the observed detrimental effects of zinc deficiency on the brain might be impaired proliferation and differentiation of stem cells participating in neurogenesis. Thus, to examine the molecular mechanisms regulating zinc metabolism and signaling in differentiating neurons, using a protocol for motor neuron differentiation, we characterized the expression of zinc homeostasis genes during neurogenesis using human induced pluripotent stem cells (hiPSCs) and evaluated the influence of altered zinc levels on the expression of zinc homeostasis genes, cell survival, cell fate, and neuronal function. Our results show that zinc transporters are highly regulated genes during neuronal differentiation and that low zinc levels are associated with decreased cell survival, altered neuronal differentiation, and, in particular, synaptic function. We conclude that zinc deficiency in a critical time window during brain development might influence brain function by modulating neuronal differentiation. |
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Institute for Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany; WG Molecular Analysis of Synaptopathies, Neurology Department, Neurocenter of Ulm University, 89081 Ulm, Germany |
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1687-5443 |
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PMID:27247802; PMCID:PMC4876239 |
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16677 |
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Wu, Y.; Tian, M.; Peng, J.; Koschan, M.; Greeley, I.; Foster, C.; Melcher, C.L. |
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On the role of Li codoping in simultaneous improvement of light yield, decay time and afterglow of Lu2SiO5:Ce3+ scintillation detectors |
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Journal Article |
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2019 |
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Phys. Status Solidi RRL |
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13 |
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1800472 |
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17768 |
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Foster, C.; Wu, Y.; Koschan, M.; Melcher, C.L. |
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Improvements in light yield and energy resolution by Li+ codoping (Lu0.75Y0.25)3Al5O12:Pr3+ single crystal scintillators |
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2018 |
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Phys. Status Solidi RRL |
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12 |
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9 |
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1800280 |
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17748 |
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